A two-way relationship between histone acetylation and metabolism.

A link between epigenetics and metabolism was initially recognized because the cellular metabolic state is communicated to the genome through the concentration of intermediary metabolites that are cofactors of chromatin-modifying enzymes. Recently, an additional interaction was postulated due to the capacity of the epigenome to store substantial amounts of metabolites that could become available again to cellular metabolite pools. Here, we focus on histone acetylation and review recent evidence illustrating this reciprocal relationship: in one direction, signaling-induced acetyl-coenzyme A (acetyl-CoA) changes influence histone acetylation levels to regulate genomic functions, and in the opposite direction histone acetylation acts as an acetate reservoir to directly affect downstream acetyl-CoA-mediated metabolism.

Yeast Nat4 regulates DNA damage checkpoint signaling through its N-terminal acetyltransferase activity on histone H4.

The DNA damage response (DDR) constitutes a vital cellular process that safeguards genome integrity. This biological process involves substantial alterations in chromatin structure, commonly orchestrated by epigenetic enzymes. Here, we show that the epigenetic modifier N-terminal acetyltransferase 4 (Nat4), known to acetylate the alpha-amino group of serine 1 on histones H4 and H2A, is implicated in the response to DNA damage in S.

Bioinformatic Analysis Reveals the Association of Human N-Terminal Acetyltransferase Complexes with Distinct Transcriptional and Post-Transcriptional Processes.

N-terminal acetyltransferases (NAT) are the protein complexes that deposit the abundant N-terminal acetylation (Nt-Ac) on eukaryotic proteins, with seven human complexes currently identified. Despite the increasing recognition of their biological and clinical importance, NAT regulation remains elusive. In this study, we performed a bioinformatic investigation to identify transcriptional and post-transcriptional processes that could be involved in the regulation of human NAT complexes.

Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis.

Histone modifications commonly integrate environmental cues with cellular metabolic outputs by affecting gene expression. However, chromatin modifications such as acetylation do not always correlate with transcription, pointing towards an alternative role of histone modifications in cellular metabolism. Using an approach that integrates mass spectrometry-based histone modification mapping and metabolomics with stable isotope tracers, we demonstrate that elevated lipids in acetyltransferase-depleted hepatocytes result from carbon atoms derived from deacetylation of hyperacetylated histone H4 flowing towards fatty acids.